Historical Information
on Paroxetine
hydrochloride
(marketed as Paxil)
Previous FDA Alerts
7/2006: The issues described
below have been
addressed in product labeling.
Increase in the Risk of Birth Defects: [Issued 12/2005]
Preliminary results of two
recent studies indicate that paroxetine increases the risk of
congenital malformations, particularly cardiovascular
malformations. Based on the new data, paroxetine’s pregnancy
category is being changed from C to D. Patients taking paroxetine
who become pregnant or who are currently in their first trimester
of pregnancy should be alerted to the potential risk to the
fetus. Discontinuing paroxetine therapy or switching to another
antidepressant should be considered for these patients. For
individual patients, however, the benefits of continuing
paroxetine may outweigh the potential risk to the fetus.
Paroxetine should generally not be initiated in women who are in
their first trimester of pregnancy or in women who plan to become
pregnant.
The FDA is currently awaiting
the final results of the recent studies and accruing additional data
pertaining to the use of paroxetine in pregnancy in order to better
characterize the risk of paroxetine. The FDA will update this sheet
as new information becomes available.
This information reflects FDA’s
preliminary analysis of data concerning this drug. FDA is
considering, but has not reached a final conclusion about this
information. FDA intends to update this sheet when additional
information or analyses become available.
Recommendations
See above
Data Summary
Preliminary analyses from two recent unpublished epidemiological
studies have shown that paroxetine use in the first trimester of
pregnancy is associated with an increased risk of specific types of
congenital malformations. In a study based on Swedish national
registry data, infants exposed to paroxetine in early pregnancy had
an approximately two-fold increased risk for cardiac defects
compared to the entire national registry population, about 2% in
paroxetine-exposed infants vs. 1% in the total population. The
majority of cardiac defects in paroxetine-exposed infants were
atrial and ventricular septal defects.
In a separate study using a United States (U.S.) insurance claims
database, infants of women who received paroxetine in the first
trimester had a 1.5-fold increased risk of cardiovascular
malformations compared to infants of women who received other
antidepressants in the first trimester, 1.5% in the paroxetine-exposed
infants vs. 1% in infants exposed to other antidepressants. The
majority of the cardiovascular defects observed in this study were
ventricular septal defects. Exposure to paroxetine in the first
trimester was also associated with an approximately two-fold higher
risk for overall congenital malformations (including cardiovascular
malformations) compared to exposure to other antidepressants in the
first trimester, about 4% vs. 2% prevalence of all congenital
malformations. Separate analyses were not done for any specific
malformations other than cardiovascular malformations.
The FDA is in the process of accruing additional data to better
characterize the risk of paroxetine.
Suicidality in Pediatric and Adult Patients [Issued
7/2005]
All patients being treated with
any type of antidepressants should be observed closely for clinical
worsening and suicidality especially during the first few months of
therapy and when the dose is modified.
Pediatrics
FDA has concluded that suicidal
thinking or behavior may increase in pediatric patients treated with
any type of antidepressant, especially early in treatment.
Increases in suicidal thinking or behavior due to drug can be
expected in about 1 out of 50 treated pediatric patients. Note that,
although paroxetine is prescribed for pediatric patients, it is not
approved by FDA for use in pediatric patients.
Adults
Several recent scientific
publications report the possibility of an increased risk for
suicidal behavior in adults who are being treated with
antidepressant medications. Even before these reports became
available, FDA began a complete review of all available data to
determine whether there is an increased risk of suicidality
(suicidal thinking or behavior) in adults being treated with any
type of antidepressant medication. It is expected that this review
will require a year or longer to complete. In the meantime, FDA is
highlighting that adults being treated with any type of
antidepressant medication, particularly those being treated for
depression, should be watched closely for worsening of depression
and for increased suicidal thinking or behavior.
This information reflects FDA’s preliminary
analysis of data concerning this drug. FDA is considering, but has
not reached a final conclusion about this information. FDA intends
to update this sheet when additional information or analyses become
available.
Recommendations
All patients being treated with any type of antidepressant for
any indication should be observed closely for clinical worsening,
suicidality, and unusual changes in behavior, especially during the
initial few months of a course of drug therapy, or at times of dose
changes, either increases or decreases. For pediatric patients, such
observation would generally include at least weekly face-to-face
contact with patients or their family members or caregivers during
the first 4 weeks of treatment, then every other week visits for the
next 4 weeks, then at 12 weeks, and as clinically indicated beyond
12 weeks. Additional contact by telephone may be appropriate between
face-to-face visits. Adults whose symptoms worsen while being
treated with antidepressant medications, including an increase in
suicidal thinking or behavior, should be evaluated by their
healthcare professional.
Consideration should be given to changing the therapeutic
regimen, including possibly discontinuing the medication, in
patients whose depression is persistently worse, or who are
experiencing emergent suicidality or symptoms that might be
precursors to worsening depression or suicidality, especially if
these symptoms are severe, abrupt in onset, or were not part of the
patient’s presenting symptoms.
Data Summary
Pooled analyses of short-term (4 to 16 weeks) placebo-controlled
trials of 9 antidepressant drugs (SSRIs and others) in children and
adolescents with MDD, obsessive compulsive disorder (OCD), or other
psychiatric disorders (a total of 24 trials involving over 4400
patients) have revealed a greater risk of adverse events
representing suicidal thinking or behavior (suicidality) during the
first few months of treatment in those receiving antidepressants.
The average risk of such events in patients receiving
antidepressants was 4 percent, twice the placebo risk of 2 percent.
No suicides occurred in these trials; however, the duration of
treatment was limited. Spontaneous post-marketing reports of
suicide-related events associated with the use of SSRIs, including
suicidal ideation, suicide attempt, self-mutilation and completed
suicide have been received. Because these events may also be related
to underlying psychiatric illness, definitive evaluation of the
effects of SSRIs on suicide related events from post-marketing
reports alone is not possible, and the data from controlled clinical
trials is more informative.
Although there are no similar comprehensive data linking the use
of antidepressant medications and an increased risk of suicidality
in adults, FDA has initiated a complete review of all available
data. FDA has asked the manufacturers of all marketed
antidepressants to identify all placebo-controlled clinical trials
conducted in adults in their development programs for their
antidepressant products, regardless of the indication studied, and
to provide information from these trials to FDA. Manufacturers are
being asked to use a similar approach to assembling this information
as was used in evaluating the risk of suicidality in
placebo-controlled trials in pediatric patients treated with
antidepressant medications.
Other Information
Report Adverse Events to
MedWatch
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Date created: July 19, 2006 |